The effects of dexamethasone, cyclosporine, and vitamin D-3 on the activation of dendritic cells stimulated by haptens

By their potent antigen-presenting function, dendritic cells (DCs) play a c rucial role in the initiation of T cell-mediated immunity, including allerg ic contact hypersensitivity. To acquire such potent antigen-presenting abil ity, DCs in tissue must be activated, with increased expression of costimul atory molecules. Recent progress in DC biology has demonstrated that DCs ca n be activated via a variety of substances, e.g. various cytokines, CD40 li gand, bacterial products, and haptens, to increase their antigen-presenting ability, probably by different mechanisms. Therefore, in this study, to el ucidate the mechanisms underlying the efficacy of the immunosuppressive dru gs dexamethasone (DEX), cyclosporine A (CY), and vitamin D-3 (Vit D3) in th e modulation of allergic contact hypersensitivity reactions, we examined th e effects of these drugs on CD86 and HLA-DR antigen expression and TNF alph a secretion by monocyte-derived DCs stimulated with two representative hapt ens, NiCl2 and DNCB, in vitro. The augmented expression of CD86 induced by NiCl2 and DNCB was significantly suppressed by DEX at concentrations in the range 10(-8) to 10(-5) M, which include concentrations less than its thera peutically effective concentration of 10(-7) M. Vit D3 also significantly s uppressed NiCl2- and DNCB-induced augmented expression of CD86, at concentr ations in the ranges 10(-9) to 10(-7) M and 10(-10) to 10(-7) M, respective ly. In contrast, significant suppressive effects of CY on the NiCl2- or DNC B-induced augmented expression of CD86 were seen only at concentrations in the range 10(-6) to 10(-5) M, which are more than ten times higher than its effective concentration for T cell suppression. The augmented expression o f HLA-DR antigen, which was only induced by stimulation with NiCl2, was res istant to treatment with these three drugs. Only DEX suppressed HLA-DR anti gen expression at 10(-5) M. TNF alpha secretion by stimulated DCs was suppr essed by DEX and Vit D3, although their effects were not statistically sign ificant. Thus DEX and Vit D3 could modulate allergic contact dermatitis by their clearly demonstrated suppressive effects on the activation of DCs by haptens.